Secondary structure of the amino-terminal region of HCV NS3 and virological response to pegylated interferon plus ribavirin therapy for chronic hepatitis C

2010 ◽  
Vol 82 (8) ◽  
pp. 1364-1370 ◽  
Author(s):  
Mai Sanjo ◽  
Takafumi Saito ◽  
Rika Ishii ◽  
Yuko Nishise ◽  
Hiroaki Haga ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Secondary Structure ◽  
Chronic Hepatitis C ◽  
Virological Response ◽  
Pegylated Interferon ◽  
Terminal Region ◽  
Amino Terminal ◽  
Pegylated Interferon Plus Ribavirin

scholarly journals IL28B CC genotype: a protective factor and predictor of the response to interferon treatment in chronic hepatitis C virus infection

2013 ◽  
Vol 154 (32) ◽  
pp. 1261-1268 ◽  
Author(s):  
Alajos Pár ◽  
Gabriella Pár ◽  
István Tornai ◽  
Ferenc Szalay ◽  
Dalma Várszegi ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Sustained Virological Response ◽  
Chronic Hepatitis C ◽  
Virological Response ◽  
Pegylated Interferon ◽  
Hepatitis C Virus Infection ◽  
Pegylated Interferon Plus Ribavirin ◽  
Chronic Hepatitis C Virus

Introduction: In chronic hepatitis C-virus infection the possible role of gene variants encoding cytokines has become the focus of interest. Aim: The aim of the study was to investigate the effect of IL28B polymorphisms on the outcome of chronic hepatitis C-virus genotype 1 infection in the Hungarian population. In addition, the association between IL28B genotypes and the Th1/Th2 cytokine production of activated peripheral blood monocytes and lymphocytes was evaluated. Method: Total of 748 chronic hepatitis C-virus genotype 1 positive patients (365 males and 383 females, aged between 18 and 82 years; mean age, 54±10 years) were enrolled, of which 420 patients were treated with pegylated interferon plus ribavirin for 24–72 weeks. Of the 420 patients, 195 patients (46.4%) achieved sustained virological response. The IL28B rs12979860 polymorphism was determined using Custom Taqman SNP Genotyping Assays (Applied Biosystems, Life Technologies, Foster, CA, USA). For cytokine studies, tumour necrosis factor-α, interleukin-2, interferon-γ, interleukin-2 and interleukin-4 production by LPS-stimulated monocytes and PMA-ionomycine activated lymphocytes were measured from the supernatant of the cells obtained from 40 hepatitis C-virus infected patients, using FACS-CBA Becton Dickinson test. The cytokine levels were compared in patients with different (CC, CT, TT) IL28B genotypes. Results: The IL28B rs12979860 CC genotype occurred in lower frequency in hepatitis C-virus infected patients than in healthy controls (26.1% vs 51.4%, OR 0.333, p<0.001). Patients carried the T allele with higher frequency than controls (73.9%, vs 48.6%, OR 3.003, p<0.001). Pegylated interferon plus ribavirin treated patients with the IL28B CC genotype achieved higher sustained virological response rate than those with the CT genotype (58.6% vs 40.8%, OR 2.057, p = 0.002), and those who carried the T allele (41.8%, OR1.976, p = 0.002). LPS-induced TLR-4 activation of monocytes resulted in higher tumour necrosis factor-α production in patients with the IL28B CC genotype compared to non-CC individuals (p<0.01). Similarly, increased tumour necrosis factor-α, interleukin-2 and interferon-γ production by lymphocytes was found in the IL28B CC carriers (p<0.01) Conclusions: The IL28B CC genotype exerts protective effect against chronic hepatitis C-virus infection and may be a pretreatment predictor of sustained virological response during interferon-based antiviral therapy. The IL28B CC polymorphism is associated with increased Th1 cytokine production of activated peripheral blood monocytes and lymphocytes, which may play a role in interferon-induced rapid immune control and sustained virological response of pegylated interferon plus ribavirin treated patients. Orv. Hetil., 2013, 154, 1261–1268.

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